Kaplan GG. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol. 2015;12:720–7.

PubMed  Google Scholar 

Garlanda C, Dinarello CA, Mantovani A. The interleukin-1 family: back to the future. Immunity. 2013;39:1003–18.

CAS  PubMed  PubMed Central  Google Scholar 

Williams MA, O’Callaghan A, Corr SC. IL-33 and IL-18 in inflammatory bowel disease etiology and microbial interactions. Front Immunol. 2019;10:1091.

CAS  PubMed  PubMed Central  Google Scholar 

Schmitz J, Owyang A, Oldham E, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005;23:479–90.

CAS  PubMed  Google Scholar 

Cayrol C, Girard JP. Interleukin-33 (IL-33): a nuclear cytokine from the IL-1 family. Immunol Rev. 2018;281:154–68.

CAS  PubMed  Google Scholar 

Eberl G, Colonna M, Di Santo JP, Mckenzie AN. Innate lymphoid cells Innate lymphoid cells: a new paradigm in immunology. Science. 2015;348:aaa6566.

PubMed  PubMed Central  Google Scholar 

Nussbaum JC, Van Dyken SJ, von Moltke J, et al. Type 2 innate lymphoid cells control eosinophil homeostasis. Nature. 2013;502:245–8.

CAS  PubMed  PubMed Central  Google Scholar 

Hodzic Z, Schill EM, Bolock AM, Good M. IL-33 and the intestine: the good, the bad, and the inflammatory. Cytokine. 2017;100:1–10.

CAS  PubMed  PubMed Central  Google Scholar 

Liew FY, Girard JP, Turnquist HR. Interleukin-33 in health and disease. Nat Rev Immunol. 2016;16:676–89.

CAS  PubMed  Google Scholar 

Luthi AU, Cullen SP, McNeela EA, et al. Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases. Immunity. 2009;31:84–98.

CAS  PubMed  Google Scholar 

Smithgall MD, Comeau MR, Yoon BR, Kaufman D, Armitage R, Smith DE. IL-33 amplifies both Th1-and Th2-type responses through its activity on human basophils, allergen-reactive Th2 cells, iNKT and NK cells. Int Immunol. 2008;20:1019–30.

CAS  PubMed  Google Scholar 

Arend WP, Palmer G, Gabay C. IL-1, IL-18, and IL-33 families of cytokines. Immunol Rev. 2008;223:20–38.

CAS  PubMed  Google Scholar 

Nishida A, Andoh A, Imaeda H, Inatomi O, Shiomi H, Fujiyama Y. Expression of interleukin 1-like cytokine interleukin 33 and its receptor complex (ST2L and IL1RAcP) in human pancreatic myofibroblasts. Gut. 2010;59:531–41.

CAS  PubMed  Google Scholar 

Martin NT, Martin MU. Interleukin 33 is a guardian of barriers and a local alarmin. Nat Immunol. 2016;17:122–31.

CAS  PubMed  Google Scholar 

Martin MU. Special aspects of interleukin-33 and the IL-33 receptor complex. Semin Immunol. 2013;25:449–57.

CAS  PubMed  Google Scholar 

Moussion C, Ortega N, Girard JP. The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel ‘alarmin’? PLoS ONE. 2008;3: e3331.

PubMed  PubMed Central  Google Scholar 

Sundlisaeter E, Edelmann RJ, Hol J, et al. The alarmin IL-33 is a notch target in quiescent endothelial cells. Am J Pathol. 2012;181:1099–111.

CAS  PubMed  Google Scholar 

Lefrancais E, Roga S, Gautier V, et al. IL-33 is processed into mature bioactive forms by neutrophil elastase and cathepsin G. Proc Natl Acad Sci USA. 2012;109:1673–8.

CAS  PubMed  PubMed Central  Google Scholar 

Lefrancais E, Duval A, Mirey E, et al. Central domain of IL-33 is cleaved by mast cell proteases for potent activation of group-2 innate lymphoid cells. Proc Natl Acad Sci USA. 2014;111:15502–7.

CAS  PubMed  PubMed Central  Google Scholar 

Cayrol C, Girard JP. The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1. Proc Natl Acad Sci USA. 2009;106:9021–6.

CAS  PubMed  PubMed Central  Google Scholar 

Cayrol C, Girard JP. IL-33: an alarmin cytokine with crucial roles in innate immunity, inflammation and allergy. Curr Opin Immunol. 2014;31:31–7.

CAS  PubMed  Google Scholar 

Bessa J, Meyer CA, de Vera Mudry MC, et al. Altered subcellular localization of IL-33 leads to non-resolving lethal inflammation. J Autoimmun. 2014;55:33–41.

CAS  PubMed  Google Scholar 

Hudson CA, Christophi GP, Gruber RC, Wilmore JR, Lawrence DA, Massa PT. Induction of IL-33 expression and activity in central nervous system glia. J Leukoc Biol. 2008;84:631–43.

CAS  PubMed  PubMed Central  Google Scholar 

Hara K, Iijima K, Elias MK, et al. Airway uric acid is a sensor of inhaled protease allergens and initiates type 2 immune responses in respiratory mucosa. J Immunol. 2014;192:4032–42.

CAS  PubMed  Google Scholar 

Kouzaki H, Iijima K, Kobayashi T, O’Grady SM, Kita H. The danger signal, extracellular ATP, is a sensor for an airborne allergen and triggers IL-33 release and innate Th2-type responses. J Immunol. 2011;186:4375–87.

CAS  PubMed  Google Scholar 

Kobori A, Yagi Y, Imaeda H, et al. Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis. J Gastroenterol. 2010;45:999–1007.

CAS  PubMed  Google Scholar 

Muzes G, Molnar B, Tulassay Z, Sipos F. Changes of the cytokine profile in inflammatory bowel diseases. World J Gastroenterol. 2012;18:5848–61.

CAS  PubMed  PubMed Central  Google Scholar 

Nemeth ZH, Bogdanovski DA, Barratt-Stopper P, Paglinco SR, Antonioli L, Rolandelli RH. Crohn’s disease and ulcerative colitis show unique cytokine profiles. Cureus. 2017;9: e1177.

PubMed  PubMed Central  Google Scholar 

Beltran CJ, Nunez LE, Diaz-Jimenez D, et al. Characterization of the novel ST2/IL-33 system in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2010;16:1097–107.

PubMed  Google Scholar 

Gundersen MD, Goll R, Hol J, et al. Loss of interleukin 33 expression in colonic crypts—a potential marker for disease remission in ulcerative colitis. Sci Rep. 2016;6:35403.

CAS  PubMed  PubMed Central  Google Scholar 

Pastorelli L, Garg RR, Hoang SB, et al. Epithelial-derived IL-33 and its receptor ST2 are dysregulated in ulcerative colitis and in experimental Th1/Th2 driven enteritis. Proc Natl Acad Sci USA. 2010;107:8017–22.

CAS  PubMed  PubMed Central  Google Scholar 

Sponheim J, Pollheimer J, Olsen T, et al. Inflammatory bowel disease-associated interleukin-33 is preferentially expressed in ulceration-associated myofibroblasts. Am J Pathol. 2010;177:2804–15.

CAS  PubMed  PubMed Central  Google Scholar 

Sedhom MA, Pichery M, Murdoch JR, et al. Neutralisation of the interleukin-33/ST2 pathway ameliorates experimental colitis through enhancement of mucosal healing in mice. Gut. 2013;62:1714–23.

CAS  PubMed  Google Scholar 

Pushparaj PN, Li D, Komai-Koma M, et al. Interleukin-33 exacerbates acute colitis via interleukin-4 in mice. Immunology. 2013;140:70–7.

CAS  PubMed  PubMed Central  Google Scholar 

Seidelin JB, Coskun M, Kvist PH, Holm TL, Holgersen K, Nielsen OH. IL-33 promotes GATA-3 polarization of gut-derived T cells in experimental and ulcerative colitis. J Gastroenterol. 2015;50:180–90.

CAS  PubMed  Google Scholar 

Imaeda H, Andoh A, Aomatsu T, et al. Interleukin-33 suppresses notch ligand expression and prevents goblet cell depletion in dextran sulfate sodium-induced colitis. Int J Mol Med. 2011;28:573–8.

CAS  PubMed  Google Scholar 

Hufford MM, Kaplan MH. A gut reaction to IL-9. Nat Immunol. 2014;15:599–600.

CAS  PubMed  PubMed Central  Google Scholar 

Duan L, Chen J, Zhang H, et al. Interleukin-33 ameliorates experimental colitis through promoting Th2/Foxp3 (+) regulatory T-cell responses in mice. Mol Med. 2012;18:753–61.

CAS  PubMed  PubMed Central  Google Scholar 

Tu L, Chen J, Xu D, et al. IL-33-induced alternatively activated macrophage attenuates the development of TNBS-induced colitis. Oncotarget. 2017;8:27704–14.

PubMed  PubMed Central  Google Scholar 

Seo DH, Che X, Kwak MS, et al. Interleukin-33 regulates intestinal inflammation by modulating macrophages in inflammatory bowel disease. Sci Rep. 2017;7:851.

PubMed  PubMed Central  Google Scholar 

Monticelli LA, Osborne LC, Noti M, Tran SV, Zaiss DM, Artis D. IL-33 promotes an innate immune pathway of intestinal tissue protection dependent on amphiregulin-EGFR interactions. Proc Natl Acad Sci USA. 2015;112:10762–7.

CAS  PubMed  PubMed Central  Google Scholar 

Hirai F, Andoh A, Ueno F, et al. Efficacy of endoscopic balloon dilation for small bowel strictures in patients With Crohn’s disease: a nationwide, multi-centre, open-label prospective cohort study. J Crohns Colitis. 2018;12:394–401.

PubMed  Google Scholar 

Nakayama T, Hirahara K, Onodera A, et al. Th2 cells in health and disease. Annu Rev Immunol. 2017;35:53–84.

CAS